To Ping ii ACKNOWLEDGEMENTS First of all, I would like to thank most sincerely my Ph.D advisor, Prof. Gary E. Christensen for his exceptional leadership, insightful guidance, wholehearted encouragement and endless enthusiasm. He is a great thinker and educator. He led me to the field of image registration and paid tremendous attention and care on my research. He introduced to me the spline model for the observational data, which turned out the foundation of the whole work. This dissertation

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... d be impossible without his help and direction. I am grateful for the support from Prof. Jeffrey F. Williamson and Prof. Martin J. Murphy of Virginia Commonwealth University. As the PI and Co-PI of PPG project (the umbrella project of this work), they were helpful in the development of the proposed image registration method, providing me with excellent clinical expertise. Special thanks to my thesis committee: Prof.